Uncontrolled hazardous waste sites (HWS) and exposure to hazardous substances continue to pose complex public health problems. This paper presents an overview of chemicals, including chemical mixtures, that have been released into environmental media in the vicinity of HWS. We describe how this type of information is being used to assess the public health implications of exposures to chemical mixtures and to develop an integrated program of applied research to more accurately characterize the potential health effects of chemical mixtures. A narrative, weight-of-evidence approach, incorporating mechanistic insights on chemical interactions is described. The utility of this information in the context of risk analysis and public health practice is discussed.